Diisopropylethylamine → 3-[5-amino-4-(4-methyl-benzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide

HRID 884777Notes

Reaction equation

C(O[C:4](=O)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](OCCN2CCOCC2)[CH:6]=1)C.[NH2:21][C:22]1[N:26]([C:27]2[CH:28]=[C:29]([CH:36]=[CH:37][C:38]=2[CH3:39])[C:30]([NH:32][CH:33]2[CH2:35][CH2:34]2)=[O:31])[N:25]=[CH:24][C:23]=1[C:40](=[O:49])C1C=CC=C(CO)C=1.C(N(C(C)C)CC)(C)C>C(O)C>[NH2:21][C:22]1[N:26]([C:27]2[CH:28]=[C:29]([CH:36]=[CH:37][C:38]=2[CH3:39])[C:30]([NH:32][CH:33]2[CH2:35][CH2:34]2)=[O:31])[N:25]=[CH:24][C:23]=1[C:40](=[O:49])[C:8]1[CH:9]=[CH:10][C:5]([CH3:4])=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 2-(4-methyl-benzoyl)-3-phenylamino-acrylonitrile 2 (205 mg, 0.78 mmol), N-cyclopropyl-3-hydrazino-4-methyl-benzamide trifluoroacetic acid salt 7 (Example 6C, 250 mg, 0.78 mmol) and diisopropylethylamine (0.14 mL, 0.78 mmol) in 8 mL of ethanol was heated at 65° C. in for 18 h. Solvent was removed and the residue was purified by silica gel column chromatography (EtOAc/hexanes, gradient from 1/3 to 3/1). The product can be further purified by trituration with Et2O to give 3-[5-amino-4-(4-methyl-benzoyl)-pyrazol-1-yl]-N-cyclopropyl-4-methyl-benzamide 3 as a white solid (64 mg, 22%). HPLC (4 minute gradient) tR 2.26 min; MS m/z 375.2 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ 8.51 (d, J=4.0, 1 H), 7.93 (d, J=8.0, 1 H), 8.51 (d, J=4.0, 1 H), 7.83 (bs, 1 H), 7.82 (s, 1 H), 7.70 (d, J=7.9, 2H), 7.53 (d, J=8.0, 1 H), 7.35 (d, J=7.9, 2 H), 6.95 (bs, 2 H), 2.86 (m, 1 H), 2.40 (s, 3 H), 2.14 (s, 3 H), 0.68 (m, 2 H), 0.56 (m, 2 H); 13C NMR (300 MHz, DMSO-d6) δ 187.4, 166.0, 151.9, 141.3, 141.1, 139.2, 136.9, 135.6, 133.0, 131.2, 129.1, 128.3, 128.0, 126.5, 102.6, 23.1, 21.0, 17.2, 5.6 ppm.

Workup

customSolvent was removed
customthe residue was purified by silica gel column chromatography (EtOAc/hexanes, gradient from 1/3 to 3/1)
customThe product can be further purified by trituration with Et2O

Sources & evidence

ORD record: ord-29fee362b7a2484cb1320b7d19a14284
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08242117B2

Reaction notes

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